CN104114151A - Excipients for nicotine-containing therapeutic compositions - Google Patents

Excipients for nicotine-containing therapeutic compositions Download PDF

Info

Publication number
CN104114151A
CN104114151A CN201280060724.4A CN201280060724A CN104114151A CN 104114151 A CN104114151 A CN 104114151A CN 201280060724 A CN201280060724 A CN 201280060724A CN 104114151 A CN104114151 A CN 104114151A
Authority
CN
China
Prior art keywords
nicotine
people
compositions
active ingredient
mixture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201280060724.4A
Other languages
Chinese (zh)
Inventor
A·J·波士克
D·小希尔顿
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Modoral Brands Inc
Original Assignee
Niconovum USA Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=47144140&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN104114151(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Niconovum USA Inc filed Critical Niconovum USA Inc
Publication of CN104114151A publication Critical patent/CN104114151A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465—Nicotine; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A61K9/0058—Chewing gums
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/34—Tobacco-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose

Abstract

A composition intended to be employed for therapeutic purposes incorporates an active ingredient (e.g., a source of nicotine) and at a non-active ingredient that is carried by a porous substrate. The non-active ingredient can be a substance that has the capability of affecting the pH of the biological system to which it is applied (e.g., basic substance and/or buffering agent is sorbed onto the porous carrier, so as to be in intimate contact with that carrier). Representative forms of nicotine include free base (e.g., as a mixture of nicotine and microcrystalline cellulose), a nicotine salt (e.g., as nicotine bitartrate) and nicotine polacrilex. The basic substance can be sodium carbonate, and the porous substrate can be microcrystalline cellulose. The composition is useful for treatment of central nervous system conditions, diseases, and disorders, and can be used as a nicotine replacement therapy.

Description

Be used for the excipient of the therapeutic combination that contains nicotine
Technical field
The present invention relates to the compositions that contains active component, described active component can be characterized as being have pharmacotoxicological effect those and can be considered to can be used for therapeutic purposes, and relate to particularly the such compositions that also contains excipient.
Background technology
Central nervous system (CNS) disease, disease or obstacle can be by drug-induced; Can be owing to genetic predisposition, infection or wound; Or can there is unknown nosetiology.They comprise methanone derivatives, nervous system disease and psychosis; And comprise neurodegenerative disease, behavior disorder, cognitive disorder and cognitive affective disorder.By the clinical manifestation of several CNS diseases, disease or obstacle owing to CNS dysfunction (, by the obstacle that causes of interacting improperly between neurotransmitter emission levels, improperly neurotransmitter receptor performance and/or neurotransmitter and neurotransmitter receptor improperly).
Nicotine such as nicotine, sample compound can affect nicotine sample acetylcholinergic receptor (nAChR).The hypotype of nAChR is present in CNS and peripheral nervous system (PNS), but the distribution of hypotype is different.For example, some hypotype is mainly present in vertebrate brain, and some other hypotype is mainly present in autonomic ganglion place, and some other its hypotype is mainly present in neuromuscular junction.Nicotine sample compound can cause neurotransmitter to discharge to the activation of nAChR.Referring to, for example, the people such as Dwoskin, Exp.Opin.Ther.Patents, 10:1561-1581 (2000); The people such as Schmitt, Annual Reports in Med.Chem., 35:41-51 (2000); The people such as Huang, J.Am.Chem.Soc., 127:14401-14414 (2006); The people such as Arneric, Biochem.Pharmacol., 74:1092-1101 (2007) and Millar, Biochem.Pharmacol., 78:766-776 (2009), they are incorporated to herein by reference.
Point out, nicotine and using of other nicotine sample compound can produce multiple pharmacotoxicological effect.Referring to, for example, the people's such as Bencherif U.S. Patent number 5,583,140; The people's such as McDonald U.S. Patent number 5,723,477; The people's such as Jacobsen U.S. Patent number 7,001,900; The people's such as Dart the people's such as U.S. Patent number 7,135,484 and Bencherif U.S. Patent number 7,214,686; People's U.S. Patent Publication No. 2010/0004451 and the U.S. Patent Application Serial 12/775,910 of Borschke such as the Ahmad that on May 7th, 2010 submits to; They are incorporated to herein by reference.As a result of, point out, nicotine and other nicotine sample compound can be used as active component and show the effectiveness in the treatment of (comprising those that affect CNS) of various disease conditions, disease and obstacle.In addition, propose, use nicotine and nicotine sample compound and treat some other disease, disease and obstacle.Referring to, for example, the people's such as Smith U.S. Patent number 5,604,231; The people's such as Bencherif U.S. Patent number 5,811,442; The people's such as Rhodes the people's such as U.S. Patent number 6,238,689 and Bencherif U.S. Patent number 6,489,349, they are incorporated to herein by reference.In addition,, helping in the work of cigarette smoker's smoking cessation, adopted use (, as the smoking cessation adminicle) of nicotine.For example, nicotine has become the active component of polytype so-called " nicotine replacement therapy " or " NRT " product.Referring to, for example, the background technology of setting forth in the people's such as Brinkley who submits on April 28th, 2010 U.S. Patent Application Serial 12/769,335, it is incorporated to herein by reference.
Propose, use nicotine with transdermal patch.The representative types of the transdermal patch product that contains nicotine is in trade name " Habitrol ", " Nicoderm ", " Nicorette ", " Nicorette CQ ", " Nicotinell " and " ProStep " lower sale.Also referring to, for example, the U.S. Patent number 4,597,961 of Etscom; The people's such as Bannon U.S. Patent number 5,298,257; The people's such as Wong U.S. Patent number 5,603,947; The people's such as Rose U.S. Patent number 5,834,011; The people's such as Osborne the people's such as U.S. Patent number 6,165,497 and Anderson U.S. Patent number 6,676,959, they are incorporated to herein by reference.Also point out, the transdermal administration of nicotine can be accompanied by the product that contains nicotine of taking in other type.Referring to, for example, the people's such as Baker U.S. Patent number 5,593,684; The U.S. Patent Publication No. 2009/0004249 of Gonda; And Fagerstrom, Health Values, 18:15 (1994), they are incorporated to herein by reference.
Provide nicotine oral administration a kind of popular especially mode, the chewing gum that contains nicotine by use.The chewing gum product that contains nicotine is in trade name " Nicorette ", " Nicotinell " and " Zonnic " lower sale.Also referring to, for example, the people's such as Ferno U.S. Patent number 3,845,217; The people's such as Lichtneckert U.S. Patent number 3,877,468; The people's such as Lichtneckert U.S. Patent number 3,901,248; The people's such as Cherukuri U.S. Patent number 6,344,222; The people's such as Pinney U.S. Patent number 6,358,060; The people's such as Ream U.S. Patent number 6,773,716, and the people's such as Pinney U.S. Patent number 6,893,654; With the U.S. Patent Publication No. 2004/0191322 of Hansson, they are incorporated to herein by reference.
For provide nicotine oral administration another kind of mode, the product of the lozenge that contains nicotine by use or tablet type.The product of the lozenge that contains nicotine, micro-lozenge, tablet and micro tablet (microtab) type is in trade name " Commit ", " Nicorette ", " Nicotinell " and " NiQuitin " lower sale.Also referring to, for example, the U.S. Patent number 5,110,605 of Acharya; 5,733,574 of Dam; The U.S. Patent number 6,280,761 of Santus; The people's such as Andersson U.S. Patent number 6,676,959, and the U.S. Patent number 6,248,760 of Wilhelmsen; The U.S. Patent Publication No. 2001/0016593 of Wilhelmsen, and the people's such as Axelsson U.S. Patent Publication No. 2010/0004294, they are incorporated to herein by reference.
Nicotine is also used with the form of nose or mouthful spray.The various exemplary mode of using the nicotine of nasal spray form, is described in: the people's such as Ferno U.S. Patent number 4,579,858; The U.S. Patent number 5,656,255 of Jones, and the U.S. Patent number 6,596,740 of Jones, they are incorporated to herein by reference.The various exemplary mode of using the nicotine of a mouthful spray form (such as using for buccal), is described in: the U.S. Patent number 6,024,097 of Von Wielligh; The people's such as Lindell U.S. Patent Publication No. 2003/0159702; The people's such as Lindell U.S. Patent Publication No. 2007/0163610 and the U.S. Patent Publication No. 2009/0023819 of Axelsson; The people's such as Lindell EP 1458388; With the people's such as Axelsson PCT WO 2008/037470, they are incorporated to herein by reference.The spray that contains nicotine is in trade name " Nicotrol NS ", " Quit " and " Zonnic " lower sale.
Propose the object for therapeutic effect is provided and used the multiple alternate manner of nicotine.For example, point out, nicotine can be mixed in following form: Orally dissolving membrane (for example, the people's such as Zerbe U.S. Patent number 6,709,671; The people's such as Leung U.S. Patent number 7,025,983; U.S. Patent number 7,491,406 with people such as Leung; With the people's such as Chan U.S. Patent Publication No. 2006/0198873, the people's such as Bess the people's such as U.S. Patent Publication No. 2006/0204559 and Lockwood U.S. Patent Publication No. 2010/0256197); Oral cavity permeability apparatus (for example, the people's such as Place U.S. Patent number 5,147,654); Gum pad (for example, the U.S. Patent number 6,319,510 of Yates); Buccal bioadhesive tablet (for example, the people's such as Houze U.S. Patent Publication No. 2006/0240087); The type form of smelling in medicated bag (pouch) or medicine bag (sachet) (for example, the people's such as Ray U.S. Patent number 4,907,605, and the people's such as Axelsson U.S. Patent Publication No. 2009/0293895); Lip pomade (for example, the U.S. Patent number 7,105,173 of Rolling) and beverage (for example, the U.S. Patent number 6,268,386 of Thompson; The U.S. Patent number 7,115,297 of Stillman, and the U.S. Patent number 7,435,749 of Knight).Also point out, can carry out delivery of nicotine (for example, the U.S. Patent number 4,284,809 of Ray by polytype suction apparatus and delivery of vapor system; The people's such as Ray U.S. Patent number 4,800,903; The people's such as Bulbrook U.S. Patent number 6,234,169, and the U.S. Patent number 6,874,507 of Farr; With the U.S. Patent Publication No. 2006/0018840 of Lechuga-Ballesteros, and the U.S. Patent Publication No. 2009/0005423 of Gonda; EP 1618803 with Hon).
Be desirable to provide and can send or use the compositions that (particularly by nose or mouthful administration) is used for the treatment of the active component of object.For example, be desirable to provide the preparation that comprises at least one active component and at least one excipient.
Summary of the invention
In one aspect, the present invention relates to comprise the compositions of at least one active component and at least one excipient.Representational active component is can be characterized as being to have pharmacotoxicological effect and can be used for the treatment of those of object.Representational active component can be the nicotine sample compound (compositions that for example, contains nicotine) (for example, nicotine sample antagonist or nicotine sample agonist) that is intended for therapeutic purposes.Described compositions has pharmaceutically acceptable form (for example, as medicine or as dietary supplement), and is most preferably suitable for nose or mouthful sends.Described compositions comprises at least one active component source and other at least one non-active ingredient.
In yet another aspect, the present invention relates to a kind of compositions, it for example, by the intimate compositions of mixtures of at least one non-active ingredient and porous carrier (, having the carrier of solid form (and preferred particulate form)).In a highly preferred embodiment, described non-active ingredient is the material with the ability of the pH that changes its biosystem of using.For example, acid material and/or buffer agent or basic matterial and/or buffer agent can be adsorbed on to small porous particle carrier (for example, microcrystalline Cellulose) upper or be otherwise provided as and the intimate contact of described small porous particle carrier.So, by using by the excipient forming with the combined basic matterial of microcrystalline Cellulose and/or buffer agent, can strengthen be suitable for nicotine sample compound Orally administered (for example, absorb for the buccal of nicotine sample compound) compositions, wherein said nicotine sample compound uses with the amount that is enough to the therapeutic effect that expectation is provided, and is used with the amount that is enough to strengthen the picked-up of nicotine sample compound in the biosystem of applying said compositions by the excipient forming with basic matterial and/or the buffer agent of microcrystalline Cellulose intimate contact.
By porous carrier being placed to and non-active ingredient intimate contact, described non-active ingredient can separate physically or separate with the nicotine in the therapeutic combination obtaining.Provide with the non-active ingredient (such as alkali or buffer agent) of porous carrier intimate contact several benefits can be provided, comprising: (1) reduce or eliminate non-active ingredient in the storage process of therapeutic combination of the present invention with unfavorable mode and nicotine component reaction or interactional ability otherwise; (2) processing ease (for example,, by the form of flowable microparticle material that such one-tenth is placed in) of raising non-active ingredient; (3) control and the measurability of the amount of the non-active ingredient that enhancing is used in therapeutic combination of the present invention.These benefits can realize in certain embodiments of the invention, still make non-active ingredient discharge or to disperse from therapeutic combination of the present invention in timely mode simultaneously.
Compositions of the present invention (comprising the compositions that contains other pharmaceutically acceptable excipient composition) can provide with the form (particularly to be applicable to the form of oral absorption, and most preferably to be applicable to the form of buccal administration of active component) that is applicable to being administered to people experimenter.The Orally administered exemplary form and the configuration that are used for the treatment of the compositions that contains nicotine of object comprise: chewing gum, tablet, lozenge, micro-lozenge, micro tablet (microtab), film and Medicinal bag type product.
Conventionally, the compositions comprising with the microcrystalline Cellulose of basic matterial and/or buffer agent intimate contact is incorporated in the preparation of at least one form that also comprises nicotine sample compound.For example, described nicotine sample compound can be nicotine, and the form of nicotine as free alkali (for example can be, as the mixture of nicotine free alkali and small porous particle carrier (such as microcrystalline Cellulose)), nicotine salt (for example, as the another kind of acylate of tartaric acid nicotine or nicotine bitartrate or nicotine), for example, as the resin complexes (, nicotine Andrea Pollack phosphorus resin (polacrilex)) of nicotine or as solvate or other applicable form.
In a particular, the invention provides a kind of pharmaceutical composition that contains nicotine, the mixture that it comprises nicotine source and porous carrier and is adsorbed on the non-active ingredient on described porous carrier, described non-active ingredient is the form that is alkali or buffer agent, and wherein said compositions is to be the mouth of described compositions or the pharmaceutically acceptable form that nose is sent of being suitable for.The alkali that described non-active ingredient normally cushions within the scope of alkaline pH or buffer agent or their combination, exemplary non-active ingredient comprises sodium carbonate, sodium bicarbonate, tertiary sodium phosphate and their combination.Based on the gross weight of described mixture, described mixture can comprise at least about the porous carrier of 70 % by weight (such as microcrystalline Cellulose) and the non-active ingredient of approximately 30 % by weight at the most.The mixture of porous carrier and non-active ingredient may further include outer protective finish, and (for example, acrylate copolymer is such as can be in trade name for all various enteric-coating materials as known in the art under obtain those).As noted above, described nicotine source can be free alkali form, and described nicotine free alkali also can be adsorbed on the second porous carrier (such as microcrystalline Cellulose).
In yet another aspect, the present invention relates to a kind of method of active component being made to disease, disease or the obstacle of response that is used for the treatment of.For example, need people experimenter's per os for the treatment of or the preparation of nasal administration effective dose by giving, can treat the disease of the stimulation therapy of nicotine sample acetylcholinergic receptor being made to response, disease or obstacle, described preparation comprises at least one nicotine sample compound and at least one excipient, described excipient is by the alkaline matter together with mixing with small porous particle carrier and/or buffer agent forms or the alkaline matter and/or the buffer agent that are carried by small porous particle carrier (for example form, nicotine with the intimate combination of compositions being formed by microcrystalline Cellulose and basic matterial and/or buffer agent).
Use the treatable exemplary disease of compositions of the present invention to depend on the active component of employing.For example, the active component that is characterized as being nicotine sample compound can be used for the treatment of various diseases and obstacle, comprises the multiple central nervous system's of impact disease and obstacle.In addition, the compositions that comprises nicotine sample compound (for example, nicotine) can be as smoking cessation adminicle.
Detailed description of the invention
The present invention will more completely be described now hereinafter.The present invention can show as many different forms, and should not be construed as and only limit to embodiment in this paper; On the contrary, provide these embodiments just in order to make present disclosure meet applicable legal requiremnt.As used in this description and claim, singulative " ", " one " and " described " comprise plural indicant, unless context clearly indicates in addition.
The present invention includes, the compositions that can be used for the treatment of object is provided.That is to say, described compositions can be used for the treatment of the reason relevant with disease or disease or symptom, or the experimenter's that described compositions uses health is otherwise provided.Described compositions can be as pharmaceutical composition or as dietary supplement.Described compositions comprises at least one active component, and described compositions can suitably be suitable for the nose of this active component or mouthful send.
A kind of particularly preferred active component is the compound that can be characterized as being nicotine sample compound.Different nicotine sample compounds and their application process are set forth in the U.S. Patent Application Serial 12/775,910 of the Borschke submitting on May 7th, 2010, and it is incorporated to herein by reference." nicotine sample compound " used herein or " nicotine source " often represent the naturally occurring or synthetic unconjugated nicotine sample compound from vegetable material, this means, described compound is by purification at least in part, and is not included in plant structure (such as Nicotiana tabacum L.).Most preferably, nicotine is naturally occurring, and as for example, obtaining from the extract of Nicotiana kind (, Nicotiana tabacum L.).Described nicotine can have the mixture of enantiomerism form S (-)-nicotine, R (+)-nicotine or S (-)-nicotine and R (+)-nicotine.Most preferably, described nicotine be following form: S (-)-nicotine (for example, with the form of all S (-)-nicotine substantially), main or most of racemic mixture being formed by S (-)-nicotine (mixture for example, being formed by S (-)-nicotine of approximately 95 weight portions and R (+)-nicotine of approximately 5 weight portions).Most preferably, described nicotine uses with in fact pure form or with substantially pure form.The nicotine very preferably using has following purity: be greater than approximately 95%, be more preferably greater than approximately 98% and be most preferably greater than approximately 99%, taking weight as basis.Although in fact nicotine can extract from Nicotiana kind, it is most preferred that, in fact or be substantially devoid of and derive from or derived from other component of Nicotiana tabacum L. described nicotine (with compositions and product produced according to the invention).
Nicotine sample compound can comprise: free alkali form, salt form, as complex or as the nicotine of solvate.Referring to, for example, the discussion of the nicotine to free alkali form in the U.S. Patent Publication No. 2004/0191322 (it is incorporated to herein by reference) of Hansson.At least a portion nicotine sample compound can use with the form of the resin complexes of nicotine, and wherein nicotine is combined in ion exchange resin (such as nicotine Andrea Pollack phosphorus resin).Referring to, for example, the people's such as Lichtneckert U.S. Patent number 3,901,248, it is incorporated to herein by reference.At least a portion nicotine can use with the form of salt.Use the U.S. Patent number 2 people such as Cox, 033,909 and the people's such as Lawson U.S. Patent number 4,830,028 and Perfetti, Beitrage Tabakforschung Int., component type and the technology in 12:43-54 (1983) (they are incorporated to herein by reference), set forth, can provide nicotine salt.The people's such as the Brinkley also submitting to referring to, on April 28th, 2010 U.S. Patent Application Serial 12/769,335, it is incorporated to herein by reference.In addition, nicotine salt can obtain from following source: such as Pfaltz and Bauer, and Inc. and K & K Laboratories, Division of ICN Biochemicals, Inc..
Exemplary pharmaceutically acceptable nicotine salt comprises the nicotine salt of following salt: tartrate (for example, tartaric acid nicotine and nicotine bitartrate), chloride (for example, nicotine hydrochloride and nicotine dihydrochloride), sulfate, perchlorate, Ascorbate, fumarate, citrate, malate, lactate, aspartate, Salicylate, toluene fulfonate, succinate, pyruvate etc.; Nicotine salt hydrate (for example, nicotine zinc chloride monohydrate) etc.Other organic acid that can form salt with nicotine comprises formic acid, acetic acid, propanoic acid, isopropylformic acid., butanoic acid, alpha-methyl butyric acid, isovaleric acid, Beta-methyl valeric acid, caproic acid, 2-furancarboxylic acid, phenylacetic acid, enanthic acid, sad, n-nonanoic acid, oxalic acid, malonic acid and glycolic and has other fatty acid of the carbochain of approximately 20 carbon atoms at the most.
In many embodiments, described nicotine sample compound exists in a variety of forms.For example, described nicotine can be used for described compositions using following form: as at least 2 kinds of salt (for example, 2 kinds of different acylates, such as the mixture of nicotine bitartrate and levulinic acid nicotine) mixture, as at least 2 kinds of salt that separate in described compositions, with free alkali form and salt form, with the free alkali form and the salt form that separate in described compositions, with salt form and with complex form (for example, resin complexes is such as nicotine Andrea Pollack phosphorus resin), with the salt form and the complex form that separate in described compositions, with free alkali form and complex form, with the free alkali form and the complex form that separate in described compositions, Deng.Like this, each single dose unit or piece (for example, chewing gum block, lozenge, medicine bag, film bar etc.) can comprise the nicotine of at least 2 kinds of forms.
Nicotine sample compound (especially conduct is compounds such as nicotine) also can be combined use with other so-called nicotiana alkaloids (, being differentiated as naturally occurring alkaloid in Nicotiana tabacum L.).For example, nicotine used according to the invention can use with nornicotine, anatabine, anabasine etc. and their combinatorial association.Referring to, for example, the people such as Jacob, Am.J.Pub.Health, 5:731-736 (1999), it is incorporated to herein by reference.
Compositions of the present invention most preferably has pharmaceutically effective and pharmaceutically acceptable form.That is to say, described compositions does not most preferably comprise or does not intentionally comprise in any appreciable degree: the tobacco ingredient except nicotine of significant quantity.Like this, pharmaceutically effective and pharmaceutically acceptable compositions does not comprise: the Nicotiana tabacum L. of part or section type, finished tobacco ingredient, or be present in traditionally the many tobacco ingredients in the tobacco product of the medicated cigarette of containing Nicotiana tabacum L., cigar, tobacco pipe or smokeless form.Comprise by extract the compositions very preferably that naturally occurring nicotine derives from Nicotiana tabacum L.: based on the gross weight of described compositions, be less than the tobacco ingredient except nicotine of 5 % by weight, more often be less than approximately 0.5 % by weight, often be less than approximately 0.25 % by weight, and the component that does not conventionally contain completely or lack the tobacco ingredient except nicotine, finished tobacco ingredient or derive from Nicotiana tabacum L..
Pharmaceutical composition of the present invention can be made easily and can obtain by unit dosage forms, therefore can prepare preparation by the common known any means of pharmaceutical field.Such preparation method comprises: (passing through several different methods) makes activating agent combined with suitable carrier or other adjuvant (it can be become to be grouped into by one or more).Then physically process the combination of active component and one or more adjuvants, for example, so that the preparation (, being configured as lozenge or tablet) of the delivery form that is suitable to be provided.
The pharmaceutical composition that contains nicotine of the present invention can comprise multiple pharmaceutically acceptable excipient." pharmaceutically acceptable excipient " refer to can for promote activating agent (for example, nicotine sample compound) storage, use and/or cure the excipient of effect.Described excipient is pharmaceutically acceptable, and its implication is, compatible with other composition of preparation, and its receptor is not had to unsuitable infringement; And they also can reduce any undesirable side effect of activating agent.Referring to, the people such as Wang, J.Parent.Drug Assn., 34 (6): 452-462 (1980), it is incorporated to herein by reference.Be suitable for being listed according to the exemplary drug excipient in compositions of the present invention: Remington:The Science & Practice of Pharmacy, the 21st edition, Lippincott Williams & Wilkins (2006); Physician ' s Desk Reference, the 64th edition, Thomson PDR (2010); With Handbook of Pharmaceutical Excipients, the 6th edition, the people such as Raymond C.Rowe compile, Pharmaceutical Press (2009), and they are incorporated to herein by reference.
Multiple excipient can change, and the selection of every kind of excipient and amount can depend on such as following factor: final form and the function of the product of needs.Referring to, for example, the preparation method of the component type of describing in following list of references, the relative quantity of composition and combination, the preparation that contains nicotine and the product that contains nicotine: the people's such as Carlsson U.S. Patent number 5,512,306; The U.S. Patent number 5,525,351 of Dam; The U.S. Patent number 5,549,906 of Santus; The people's such as Reiner U.S. Patent number 5,711,961; The U.S. Patent number 5,811,126 of Krishnamurthy; The people's such as Albrechtsen U.S. Patent number 5,939,100; The people's such as Khankari U.S. Patent number 6,024,981; The people's such as Humbert-Droz U.S. Patent number 6,083,531; Gowan, the people's such as Jr. U.S. Patent number 6,090,401; The U.S. Patent number 6,110,495 of Dam; The U.S. Patent number 6,248,760 of Wilhelmsen; The U.S. Patent number 6,280,761 of Santus; The people's such as Ream U.S. Patent number 6,426,090; The people's such as Patel U.S. Patent number 6,569,463; The people's such as Smith U.S. Patent number 6,583,160; The people's such as Moro U.S. Patent number 6,585,997; The people's such as Andersson U.S. Patent number 6,676,959; The people's such as Pinney U.S. Patent number 6,893,654; The people's such as Leung U.S. Patent number 7,025,983, and etc. people's U.S. Patent number 7,163,705; The people's such as Andersson U.S. Patent Publication No. 2003/0176467; The people's such as Martino U.S. Patent Publication No. 2003/0235617; The people's such as Vaya U.S. Patent Publication No. 2004/0096501; The people's such as Liu U.S. Patent Publication No. 2004/0101543; The U.S. Patent Publication No. 2004/0191322 of Hansson; The people's such as Ek U.S. Patent Publication No. 2005/0053665; The people's such as Chan U.S. Patent Publication No. 2005/0123502; The people's such as Andersen U.S. Patent Publication No. 2008/0038209; The people's such as Andersson U.S. Patent Publication No. 2008/0286341; The U.S. Patent Publication No. 2009/0023819 of Axelsson; The U.S. Patent Publication No. 2009/0092573 of Andersen; The people's such as Axelsson U.S. Patent Publication No. 2010/0004294, and the people's such as Axelsson U.S. Patent Publication No. 2010/0061940, they are incorporated to herein by reference.The people's such as the Brinkley also submitting to referring to, on April 28th, 2010 U.S. Patent Application Serial 12/769,335, it is incorporated to herein by reference.
The representative excipient type that is particularly useful for the production of the product that contains nicotine comprises: the filler of active component or carrier (for example, calcium polycarbophil, microcrystalline Cellulose, corn starch, silicon dioxide or calcium carbonate), thickening agent, film forming agent and binding agent (for example, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, arabic gum, sodium alginate, xanthan gum and gelatin), buffer agent and pH controlling agent (for example, magnesium oxide, magnesium hydroxide, potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate or its mixture), antitack agent (for example, Talcum), fluidizer (for example, silica sol), natural or artificial sweeting agent (for example, glucide, acesulfame potassium, aspartame, sucralose, hydroxyl isomaltulose, lactose, mannitol, sorbitol, xylitol and sucrose), wetting agent (for example, glycerol), antiseptic and antioxidant (for example, sodium benzoate and ascorbyl palmitate), surfactant (for example, polyoxyethylene sorbitan monoleate), natural or artificial correctives (for example, Herba Menthae, Cortex cinnamomi japonici (Ramulus Cinnamomi), Fructus Pruni pseudocerasi or other fruit correctives), dyestuff or pigment (for example, titanium dioxide or D & C Yellow No.10) and lubricant or processing aid (for example, calcium stearate or magnesium stearate).The product that contains nicotine of some type also can have outer coatings, described outer coatings is grouped into (for example, outer coatings can be by forming such as following compositions: lac, glazing composition and the glazing agent of Brazil wax and pharmaceutically acceptable form) by the one-tenth that acceptable outer coatings can be provided.
Comprise nicotine and can there is polytype form and configuration as the representative compositions of active component, and therefore, the characteristic of described compositions, character, performance, denseness, shape, form, size and weight can change.The shape of representative compositions can be spherical, cylindrical (for example, the general shape from the general shape of flat-disk to relatively long and thin rod), spiral type, Citrus (obloid), square, rectangle etc. conventionally; Or described compositions can have the forms such as pearl, nodular powder, crystalline powder, capsule, sheet, band, gel.The shape of described compositions can be similar to the product of multiple pill, tablet, lozenge, micro-lozenge, capsule, capsule sheet, micro tablet (microtab), medicated bag and chewing gum type, and described product is traditionally for drug administration series products.The general aspects of representative compositions can have soft or hard touch sense, or has middle flexibility or hardness; Like this, can think that described compositions is malleable, soft, resistance to that chew, resilient, crisp etc.When Orally administered, can think that the various components of described product can easily be disperseed or be disperseed lentamente, or those different components can be dissolved with different speed (for example,, from relatively very fast to relatively slow).As a result of, for the compositions of taking in by the mouth of putting into people experimenter, the rate of release of active component between the product operating period can change to relatively slow from relatively very fast, this depends on such as following factor: the design of product, and use the experimenter of this product to the use of product.As an example, also referring to the product type proposing in following list of references: the people's such as Ray U.S. Patent number 4,655,231; The people's such as Place U.S. Patent number 5,147,654; The people's such as Carlsson U.S. Patent number 5,543,424; The U.S. Patent number 6,268,386 of Thompson; The U.S. Patent number 6,319,510 of Yates; The people's such as Halliday U.S. Patent number 6,488,953; The people's such as Zerbe U.S. Patent number 6,709,671; The people's such as Leung U.S. Patent number 7,025,983; The U.S. Patent number 7,105,173 of Rolling; The U.S. Patent number 7,115,297 of Stillman; The U.S. Patent number 7,435,749 of Knight, and the people's such as Leung U.S. Patent number 7,491,406; U.S. Patent Publication No. 2004/0191322 with Hansson; The people's such as Chan U.S. Patent Publication No. 2006/0198873; The people's such as Houze U.S. Patent Publication No. 2006/0240087; The people's such as Bess U.S. Patent Publication No. 2006/0204559; The people's such as Steen U.S. Patent Publication No. 2007/0269492; The people's such as Chau U.S. Patent Publication No. 2008/0020050; The people's such as Andersson U.S. Patent Publication No. 2008/0286340; The people's such as Sanghvi U.S. Patent Publication No. 2008/0292683, and the people's such as Bunick U.S. Patent Publication No. 2009/0004248, they are incorporated to herein by reference.
Preparation of the present invention can comprise short-term, start fast, departs from fast (rapid-offset), controlled release, sustained release, delayed release and pulsation-releasing preparation, thereby the preparation of using of realizing active component is provided.Also referring to, Remington ' s Pharmaceutical Sciences, the 18th edition; Mack Publishing Company, Eaton, Pennsylvania, (1990), it is incorporated to herein by reference.
Can prepare solid dosage forms, thereby the delayed release of activating agent (, nicotine sample compound) is provided, for example, by applying coating.Delayed release coating is known in the art, and the dosage form that contains them can be prepared by any known proper method.Such method generally includes: for example, after preparation solid dosage forms (, tablet or capsule sheet), apply delayed release coating compositions.Applying of coating can be by the method such as such as depletion of QI coating, fluidized bed coating, use coating pan.Material as delayed release coating can be polymerization in nature, for example, such as polymer and copolymer and the ester thereof of fibrous material (, cellulose butyrate phthalic acid ester, hydroxypropylmethyl cellulose phthalate and carboxymethylethylcellulose) and acrylic acid, methacrylic acid.
According to solid dosage forms of the present invention also can sustained release (, release bioactive agent in long-time section), also can yes or no delayed release.Extended release preparation is known in the art, and is conventionally prepared as follows: active component is dispersed in the substrate of material (such as insoluble plastics, hydrophilic polymer or fatty compound) that can degrade gradually or hydrolysis.Alternatively, can be to the coated such material of solid dosage forms.
Can change for mode and the method for preparing and producing described compositions.The representative condition relevant with the production of medicine type product comprises: control heat and temperature (, the temperature that various compositions exposed in process of production and the temperature of production environment), water capacity (for example, the moisture existing in single composition and in final composition), the air-flow that experiences in process of production of humidity, atmosphere control (for example, blanket of nitrogen), various composition in production environment and the factor of other similar type.In addition, each procedure of processing relating in production can comprise: select some solvent and processing aid, use heat and radiation, freezing and cryogenic conditions, composition composite rate etc.For example, due to concentration of the composition of the granularity of the composition of the selection of the form (, solid, liquid or gas) of various compositions, solid form or crystallographic property, liquid form etc., also can control described working condition.By such as extruding, pressurize, the technology such as spraying, composition can be processed into the compositions of hope.
Carrier and non-active ingredient are combined to form as according to the intimate mixture of excipient of the present invention.Described non-active ingredient is most preferably the material with the ability of the pH that changes its biosystem of using.The carrier of this non-active material can change.Described carrier is most preferably small porous particle carrier material, such as microcrystalline cellulose material, silicon dioxide or calcium silicates.The example of microcrystalline cellulose cellulosic material is: those (for example, grade DG, CE-15, HFE-102, PH-100, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300 and PH-302) that obtained from FMC Corporation under trade name Avicel; Derive from the Vivapur (for example, grade 12,14, XLM200,101,102,103,105,112,200,301 and 302) of JRS PHARMA GmbH & Co.KF; (for example derive from the Vivacel of J.Rettenmaier & Sohne GmbH, grade 12,20,101 and 102) and derive from the Emocel (for example, class 5 0M, 90M, LM50, XLM90, HD90 and LP200) of JRS PHARMA GmbH & Co.KF.Also referring to, for example, the type of the micro crystal material of elaboration in the U.S. Patent Publication No. 2004/0191322 of Hansson and the EP 1578422 of Hansson (they are incorporated to herein by reference).The particle size of small porous particle carrier material (for example, microcrystalline Cellulose) can change, and some representational material has at approximately 15 microns to the particle size within the scope of approximately 250 micron diameters.
Described non-active ingredient is the compositions that is different from active component in chemical constitution, and described active component and its combination are to provide according to therapeutic combination of the present invention.In certain embodiments, described non-active ingredient is alkali or buffer agent or their combination cushioning within the scope of alkaline pH.In other embodiments, described non-active ingredient is acid or buffer agent or their combination cushioning within the scope of acid pH.
Described non-active ingredient alkaline matter can change.Exemplary highly basic be sodium hydroxide, potassium hydroxide, and composition thereof.Exemplary weak base be sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and composition thereof.Also referring to, the dissimilar buffer agent of elaboration in the people's such as Lindell EP 1458388 (it is incorporated to herein by reference).(for example combine in intimate contact mode with carrier, be adsorbed on small porous particle material (such as microcrystalline Cellulose)) non-active ingredient can as single component (for example, as sodium hydroxide or as sodium bicarbonate) or for example, as the combination of at least 2 kinds of compositions the mixture of sodium carbonate and sodium bicarbonate (, as).In addition, (for example combine in intimate contact mode with carrier, on being adsorbed on materials such as microcrystalline Cellulose) non-active ingredient can as single buffer composition (for example, as sodium dihydrogen phosphate) or for example, as the combination of at least 2 kinds of compositions the mixture of sodium carbonate and sodium dihydrogen phosphate (, as).
Described non-active ingredient acidic materials can change.Exemplary acid material comprise citric acid, malic acid, oxalic acid, levulic acid, and composition thereof.Exemplary buffer agent comprises sodium citrate, sodium acetate, monopotassium phosphate etc.(for example combine in intimate contact mode with carrier, be adsorbed on small porous particle material (such as microcrystalline Cellulose)) non-active ingredient can as single component (for example, as citric acid or as malic acid) or for example, as the combination of at least 2 kinds of compositions the mixture of malic acid and citric acid (, as).In addition, (for example combine in intimate contact mode with carrier, on being adsorbed on materials such as microcrystalline Cellulose) non-active ingredient can as single buffer composition (for example, as sodium citrate) or for example, as the combination of at least 2 kinds of compositions the mixture of sodium citrate and citric acid (, as).
The amount that is adsorbed on the non-active ingredient (for example, basic matterial and/or buffer agent or acid material and/or buffer agent) on carrier or base material can change.Conventionally the base material (, small porous particle carrier material) that, serves as the carrier of basic matterial and/or buffer agent (or acid material and/or buffer agent) is the advantage component (by weight) of the mixture that obtains.Conventionally, combination weight (or combination weight of base material and acid material and/or buffer agent) based on base material and basic matterial and/or buffer agent, described base material account for mixture weight at least about 70%, conventionally at least about 80%, often at least about 90% with usually at least about 95%; The simultaneously combination weight (or combination weight of base material and acid material and/or buffer agent) based on base material and basic matterial and/or buffer agent, the amount of basic matterial and/or buffer agent conventionally account for mixture weight at the most approximately 30%, conventionally at least about 20%, often at the most approximately 10% and usually at the most approximately 5%.
The mode that non-active ingredient basic matterial and/or buffer agent (or acid material and/or buffer agent) are adsorbed on base material can change.For example, use the technology of the type of elaboration in the improved U.S. Patent Application Publication No. 2004/0191322 at Hansson (its be incorporated to by reference herein) suitably, can produce the intimate mixture of each composition.Conventionally, non-active ingredient is dissolved or (is for example dispersed in suitable liquid, different solvents is such as liquid, the water/alcoholic solution etc. with aqueous nature) in, liquid solution or dispersion and particulate carrier material are contacted with each other, and (for example remove liquid,, vacuum drying dry by spraying, air-dry, heating etc.), thus solid material is provided.It is most preferred that, the intimate mixture of the non-active ingredient obtaining and particulate carrier does not comprise the active component that (, being substantially devoid of) intention combines with described intimate mixture in the preparation of final therapeutic combination.
A kind of method that specially suitable production is adsorbed on the mixture of non-active ingredient alkaline matter on perforated substrate and/or buffer agent comprises: provide alkaline matter and/or the buffer agent solution in liquid flux so that solution to be provided, the base material of porous is provided, combine described base material and liquid solution, and the solvent of removing the mixture obtaining is to provide dry solid mixture.Described liquid normally has the liquid of aqueous nature.Often, can to the liquid solution that will combine and substrate mixes and/or slightly higher than the heating of environmental condition.Conventionally, use spray technique, liquid can be put on to substrate.In addition, desirable, stirring, rolling, shake or otherwise mixing (for example, using pan coating machine, tumble mixer, shearing stirrer etc.) substrate, make liquid solution and substrate contact with each other simultaneously, so as assisted Extraction solution is based for liquid evenly applies.Often, can remove liquid by dry technology, and can mixture be heated to the temperature slightly higher than environment in dry run.
In certain embodiments, before being incorporated in the compositions that contains nicotine, can further process the mixture of the non-active ingredient of porous carrier and absorption.For example, coating material can be put on to described mixture, to provide protective barrier to strengthen bin stability, dissolution or absorbent properties etc. with the non-active material that changes absorption after being ingested.Exemplary coating material comprises acrylic polymer compositions, such as can be in trade name under derive from those of Evonik Industries AG.
For example, can change for mode and method that the excipient materials material of the intimate compositions of mixtures of microcrystalline Cellulose and basic matterial and/or buffer agent (, by) is mixed in the compositions that contains nicotine.The position of excipient materials in the described compositions that contains nicotine also can change.Described excipient materials can be dispersed throughout in described therapeutic combination or preparation, or the selection area that is positioned at described preparation (for example, be dispersed throughout equably in described compositions, in the outer coatings of described compositions, or in the region being occupied by nicotine of described compositions, or in the selected layer of the compositions of layering).Like this, some region of described preparation can be substantially devoid of excipient materials, or can in described preparation or everywhere, have the Concentraton gradient of excipient materials, or certain region of described preparation can have excipient materials concentration relatively high compared with other region of said preparation.Can coextrusion, lamination or the formation compositions that contains nicotine, thereby there is sandwich type form; And therefore can control the position of nicotine, excipient materials and other composition, thus the characteristic of hope is provided, such as performance, behavior (behavior), with the interaction of other composition or without interaction, bin stability etc.In addition, can and (for example be produced into core/shell mould configuration by the mixture preparation of component composition, there is an interior zone and at least one extra outer field chewing gum or lozenge type product), the regional of such product has different total composition or character.Thereby for example, described excipient materials can have relatively high concentration at the interior zone of product, or has relatively high concentration in the perimeter of product.
In use, compositions of the present invention is used to be applicable to the form that buccal, Sublingual or nose send conventionally.In certain embodiments, described compositions is the form that is particularly suitable for oral absorption.For example, be generally used for using the chewing gum that contains nicotine, lozenge and the medicated bag product of traditional type and mode and the method for less preferred spray far away although use, can use and use the compositions that contains nicotine.
Comprise nicotine as active component and the representative compositions of a kind of particularly preferably type of the nicotine of non-suction form is provided, thering is the form of the same masticable product of chewing gum or other type.The product of gum formats comprises that chewing gum base (for example, typically, the type of the pharmaceutically acceptable chewing gum base that can obtain from following source: such as Gum Base Co.S.p.a., Wm.J.Wrigley Jr.Company or Gumlink A/S).Referring to, for example, type, chewing-gum preparation, gum formats and the configuration of the chewing gum that contains nicotine of describing in following list of references, chewing gum feature and for preparing or produce the technology of chewing gum: the people's such as Ferno U.S. Patent number 3,845,217; The people's such as Lichtneckert U.S. Patent number 3,877,468; The people's such as Lichtneckert U.S. Patent number 3,901,248; The people's such as Song U.S. Patent number 5,154,927; The people's such as Ream U.S. Patent number 6,322,806; The people's such as Cherukuri U.S. Patent number 6,344,222; The people's such as Ream U.S. Patent number 6,355,265; The people's such as Pinney U.S. Patent number 6,358,060; The people's such as Ream U.S. Patent number 6,773,716; The people's such as Pinney U.S. Patent number 6,893,654; The people's such as Athanikar U.S. Patent number 7,101,579; The people's such as Johnson U.S. Patent number 7,163,705, and the people's such as Norman U.S. Patent number 7,208,186; The people's such as Lindell U.S. Patent Publication No. 2004/0194793; The people's such as Andersen U.S. Patent Publication No. 2006/0099300; The people's such as Andersen U.S. Patent Publication No. 2006/0121156; The people's such as Andersen U.S. Patent Publication No. 2006/0165842; The U.S. Patent Publication No. 2006/0204451 of Salini; The people's such as Andersen U.S. Patent Publication No. 2006/0246174; The people's such as Mody U.S. Patent Publication No. 2006/0275344; The people's such as Cherukuri U.S. Patent Publication No. 2007/0014887; The people's such as Steen U.S. Patent Publication No. 2007/0269386; The U.S. Patent Publication No. 2009/0092573 of Andersen, and the people's such as Axelsson U.S. Patent Publication No. 2010/0061940; They are incorporated to herein by reference.The amount of the compositions containing at the chewing gum type product of every or per unit can change.For example, the common weight of the typical flat of chewing gum product is at least about 0.5g, often at least about 1g, often at least about 1.5g; The weight of the typical flat of simultaneously such product is no more than about 3g conventionally, is often no more than about 2.5g, is often no more than about 2g.The chewed time period of chewing gum block can change; Conventionally, chew every chewing gum at least about 5 minutes, often at least about 10 minutes, conventionally chew every chewing gum simultaneously approximately 40 minutes at most, often maximum approximately 30 minutes.
Comprise nicotine as active component and the particularly preferably representative compositions of type of another kind of the nicotine of non-suction form is provided, thering is the form of lozenge, micro-lozenge, tablet, micro tablet or other tablet form product.Referring to, for example, the type of the lozenge that contains nicotine of describing in following list of references, lozenge preparation, lozenge form and configuration, lozenge feature and for preparing or produce the U.S. Patent number 4,967,773 of the technology of lozenge: Shaw; The U.S. Patent number 5,110,605 of Acharya; The U.S. Patent number 5,733,574 of Dam; The U.S. Patent number 6,280,761 of Santus; The people's such as Andersson U.S. Patent number 6,676,959; The U.S. Patent number 6,248,760 of Wilhelmsen, and the people's such as Chen U.S. Patent number 7,374,779; The U.S. Patent Publication No. 2001/0016593 of Wilhelmsen; The people's such as Liu U.S. Patent Publication No. 2004/0101543; The U.S. Patent Publication No. 2006/0120974 of Mcneight; The people's such as Chau U.S. Patent Publication No. 2008/0020050; The people's such as Gin U.S. Patent Publication No. 2009/0081291, and the people's such as Axelsson U.S. Patent Publication No. 2010/0004294; With the people's such as Carlsson PCT WO 91/09599, they are incorporated to herein by reference.The amount of the present composition containing at the lozenge type product of every or per unit can change.For example, the common weight of the typical flat of lozenge product is at least about 100mg, often at least about 200mg, often at least about 300mg; The weight of the typical flat of simultaneously such product is no more than about 1.5g conventionally, is often no more than about 1g, is often no more than about 0.75g.
Comprise nicotine as active component and the particularly preferably representative compositions of type of another kind of the nicotine of non-suction form is provided, thering is the form of medicated bag or medicine bag type product.Referring to, for example, the type of the medicated bag material of describing in the people's such as Axelsson U.S. Patent Publication No. 2009/0293895 (it is incorporated to herein by reference) and the preparation that contains nicotine.Also referring to, for example, the type of the medicated bag material of describing in the people's such as Brinkley U.S. Patent Publication No. 2010/0018539 (it is incorporated to herein by reference) and medicated bag production technology (for example, medicated bag filling and Sealing Technology).The amount of the compositions containing at each medicated bag can change.For example, representational medicated bag product conventionally contain at least about 75mg, often at least about 100mg, often at least about 150mg according to compositions of the present invention; Meanwhile, the amount of the compositions containing in single representative medicated bag is no more than about 500mg conventionally, is often no more than about 400mg, is often no more than about 300mg.
The amount of the active component in total composition can change.With regard to intention by the compositions putting into experimenter's mouth and carry out oral consumption (for example, can chew chewing gum product, lozenge, medicated bag product of piece etc.), the amount of the nicotine in each dosage piece or unit is normally at least about 0.5mg, normally 1mg at least, being often at least about 1.5mg, is often at least about 2mg; The amount of the nicotine in every is no more than about 10mg conventionally simultaneously, is conventionally no more than about 8mg, is often no more than about 6mg, is often no more than about 5mg, is calculated as nicotine substrate.The exemplary types of such product can every or unit comprise about 2mg, about 2.5mg, about 3mg, about 3.5mg and about 4mg nicotine, be calculated as nicotine substrate.
Comprise nicotine has spray form as the atypical representative compositions of active component.Conventionally, such spray is applied in nose or mouth, absorbs for per nasal or oral mucous membrane, and this is contrary with steam or thin aerosol in suction lung.Referring to, for example, the type of the spray material of describing in following list of references and the spray preparation that contains nicotine: the people's such as Ferno U.S. Patent number 4,579,858; The U.S. Patent number 5,656,255 of Jones; The U.S. Patent number 6,024,097 of Von Wielligh, and the U.S. Patent number 6,596,740 of Jones; The people's such as Lindell U.S. Patent Publication No. 2003/0159702; The people's such as Lindell U.S. Patent Publication No. 2007/0163610, and the U.S. Patent Publication No. 2009/0023819 of Axelsson; The people's such as Lindell EP 1458388; With the people's such as Axelsson PCT WO 2008/037470, they are incorporated to herein by reference.Preferred spray product uses producing aerocolloidal device by machinery and producing spraying or mist of aerosol apparatus or other type.Preferred spray product adopts liquid flux or the carrier (for example, water or water/alcohol mixture) of the intimate mixture that contains nicotine and basic matterial and particulate carrier; And it is most preferred that, those preparations before using by shake or otherwise stir.Nicotinic density in liquid spray agent formulation can change, but normally approximately 0.5% to approximately 5%, often approximately 1% to approximately 3% scope, this gross weight based on liquid preparation, and be calculated as nicotine substrate.
Although compositions of the present invention is preferably non-suction, use is designed to bioactive agent delivery to deliver to dissimilar suction apparatus and the delivery of vapor system of lung (sending contrary with buccal, Sublingual or nose), may prepare with the form of can lung sending the combination of the intimate mixture of the nicotine sample compound pointed out and particulate carrier and non-active ingredient basic matterial and/or buffer agent above.Referring to, for example, the U.S. Patent number 4,284,809 of the preparation sucking of describing in following list of references and the type of delivery of vapor device and system: Ray; The people's such as Ray U.S. Patent number 4,800,903; The people's such as Turner U.S. Patent number 5,167,242; The people's such as Turner U.S. Patent number 6,098,632; The people's such as Bulbrook U.S. Patent number 6,234,169, and the U.S. Patent number 6,874,507 of Farr; The people's such as Warchol U.S. Patent Publication No. 2004/0034068; The U.S. Patent Publication No. 2006/0018840 of Lechuga-Ballesteros; The people's such as Andersson U.S. Patent Publication No. 2008/0302375, and the U.S. Patent Publication No. 2009/0005423 of Gonda; With the EP 1618803 of Hon, they are incorporated to herein by reference.
The dosage of active component (, all various nicotine forms) is such amount: it treats some symptoms of disease, disease or obstacle that experimenter or patient suffer effectively, or prevents the appearance of described symptom." effective dose ", " therapeutic dose " or " effective dose " refer to such amount: it is enough to cause pharmacology or the therapeutic effect of hope, thereby produce effective prevention or the treatment of described disease, disease or obstacle.Thereby, the effective dose of active component is such amount: its domain of dependence that is enough to enter health (for example, comprise the blood brain barrier through experimenter), be combined in the relevant acceptor site in experimenter's CNS and PNS, and/or (for example cause neuro pharmacology effect, cause neurotransmitter secretion, thereby produce effective prevention or the treatment of described disease, disease or obstacle).The prevention of described obstacle shows as, and for example, postpones the outbreak of the symptom of disease, disease or obstacle.The treatment of described obstacle shows as, for example, and the minimizing of the symptom relevant with disease, disease or obstacle, or the improvement of the recurrence of its symptom.
With regard to compositions of the present invention, the expection daily dose of active component can change.The accumulated dose of active component can depend on such as following factor: the body weight of taking in the experimenter of described compositions, the type of disease, disease or the obstacle for the treatment of, state or the seriousness of disease, disease or the obstacle for the treatment of, the pharmacotoxicological effect of hope, or other such factor.Conventionally, the amount of the nicotine active component of using to experimenter every day (being calculated as nicotine substrate) is at least about 2mg, is often at least about 4mg, is often at least about 10mg.Conventionally, the amount of the nicotine active component of using to experimenter every day is no more than about 60mg, is often no more than about 50mg, is often no more than about 40mg.Also referring to, for example, dosage regimen type and the medicine-feeding technology in following list of references, described: the people's such as Baker U.S. Patent number 5,593,684, and the people's such as Kyle U.S. Patent number 6,660,754; U.S. Patent Publication No. 2004/0006113 with Sachs; The people's such as Pinney U.S. Patent Publication No. 2005/0214229; The U.S. Patent Publication No. 2008/0124283 of Andersen, and the people's such as Axelsson U.S. Patent Publication No. 2009/0293895; They are incorporated to herein by reference.
Various disease conditions, disease and the obstacle of response made in the stimulation that compositions of the present invention can be used for the treatment of the nicotine sample acetylcholinergic receptor (nAChR) to one or more types.Described compositions can be used for the treatment of disease, disease and the obstacle reported by using or use medicable those types of nicotine (as the agonist of nAChR), such as neurodegenerative disease, behavior disorder, cognitive disorder and cognitive affective disorder.Like this, described compositions can be used for the treatment of various CNS disease, disease and obstacle, and described compositions also can be as the product that contains nicotine, such as smoking cessation adminicle (, as NRT component).
Following embodiment is the example that can be used for the representative embodiment of the present invention (such as NRT) of the oral absorption of nicotine that is provided for therapeutic purposes, and still described embodiment should not be construed as and limits the scope of the invention.
Embodiment 1
Provide about 180ml deionized water in room temperature.In this water, dissolve approximately 20 grams of sodium hydroxide.Like this, obtain 10% sodium hydrate aqueous solution.
The microcrystalline Cellulose that acquisition is obtained commercially.Described microcrystalline Cellulose can derive from JRS PHARMA GmbH & Co.KF under trade name Vivapur101.The microcrystalline Cellulose of about 9.9g dried forms is provided in room temperature, and applies approximately 1 gram of 10% sodium hydroxide solution by spraying to this dry particles.Use Nalgene Aerosol Spray Bottle Cat.No.2430-0200 that sodium hydroxide solution is sprayed in dry particles, described microgranule is mixed simultaneously, like this solution is put on to described microgranule equably.Then, mixture is air-dry in room temperature, to obtain having the desciccate of approximately 10 gram weight.The first sample of the microcrystalline Cellulose obtaining and the intimate mixture of sodium hydroxide, for white, is made up of approximately 99 parts of microcrystalline Cellulose and approximately 1 part of sodium hydroxide, and is that be dried, free-pouring, fine powdered material.The representational excipient obtaining be substantially pure (, described intimate mixture is made up of microcrystalline Cellulose and sodium hydroxide, and be substantially devoid of other excipient materials and this excipient can together with the active component of the therapeutic combination that combines).Can easily operate (for example, in order to store, to weigh, mixing etc.) representative excipient as excipient, and can combine with other excipient and use and combine use with the active ingredient components of therapeutic combination.
Except approximately 9.8 grams of microcrystalline Cellulose have approximately 2 grams of aforementioned sodium hydroxide solutions that apply to it, with for providing the first sample substantially the same mode, the second sample of being formed by microcrystalline cellulose cellulosic material of preparation.The second sample of the microcrystalline Cellulose obtaining and sodium hydroxide material, for white, is made up of approximately 98 parts of microcrystalline Cellulose and approximately 2 parts of sodium hydroxide, and is that be dried, free-pouring, fine powdered material.
Use Fisher Science Education pH Meter 510Series, at the pH of indoor temperature measurement 50ml deionized water, and the pH of definite water is 6.93.
Approximately 2.5 grams of microcrystalline Cellulose are mixed in about 50ml deionized water, and after mixing, within approximately 1 minute, measure the pH of this liquid mixture.Determine that the mixture obtaining is 5.96 at the pH of room temperature.
The first sample of approximately 2.5 grams of microcrystalline Cellulose and sodium hydroxide is mixed in about 50ml deionized water, and after mixing, within approximately 1 minute, measure the pH of this liquid mixture.Determine that the mixture obtaining is 11.01 at the pH of room temperature.
The second sample of approximately 2.5 grams of microcrystalline Cellulose and sodium hydroxide is mixed in about 50ml deionized water, and after mixing, within approximately 1 minute, measure the pH of this liquid mixture.Determine that the mixture obtaining is 11.12 at the pH of room temperature.
The solution of levulic acid in water is provided.In being joined deionized water by room temperature, enough levulic acids contain to provide the 1% levulinic aqueous acid of having an appointment.At the pH of this solution of indoor temperature measurement, and be defined as 3.28
Approximately 2.5 grams of microcrystalline Cellulose are mixed in the aforementioned levulic acid aqueous solution of about 50ml, and mixing the pH that later measures liquid mixture for approximately 1 minute.Determine that the mixture obtaining is 3.33 at the pH of room temperature.
The first sample of approximately 2.5 grams of aforementioned microcrystalline Cellulose and sodium hydroxide is mixed in the aforementioned levulic acid aqueous solution of about 50ml, and mixing the pH that later measures liquid mixture for approximately 1 minute.Determine that the mixture obtaining is 9.00 at the pH of room temperature.
The second sample of approximately 2.5 grams of aforementioned microcrystalline Cellulose and sodium hydroxide is mixed in the aforementioned levulic acid aqueous solution of about 50ml, and mixing the pH that later measures liquid mixture for approximately 1 minute.Determine that the mixture obtaining is 10.04 at the pH of room temperature.
Embodiment 2
Provide about 180ml deionized water in room temperature.In this water, dissolve approximately 20 grams of sodium carbonate.Like this, obtain 10% aqueous sodium carbonate.
The microcrystalline Cellulose that acquisition is obtained commercially.Described microcrystalline Cellulose can derive from JRS PHARMA GmbH & Co.KF under trade name Vivapur101.The microcrystalline Cellulose of about 9.5g dried forms is provided in room temperature, and applies approximately 5 grams of 10% sodium carbonate liquors by spraying to this dry particles.Use Nalgene Aerosol Spray Bottle Cat.No.2430-0200 that described sodium carbonate liquor is sprayed in described dry particles, described microgranule is mixed simultaneously, like this solution is put on to described microgranule equably.Then at drying at room temperature mixture, to obtain having the desciccate of approximately 10 gram weight.The sample of the microcrystalline Cellulose obtaining and the intimate mixture of sodium carbonate, for white, is made up of approximately 95 parts of microcrystalline Cellulose and approximately 5 parts of sodium carbonate, and is that be dried, free-pouring, fine powdered material.The representational excipient obtaining be substantially pure (, described intimate mixture is made up of microcrystalline Cellulose and sodium carbonate, and be substantially devoid of other excipient materials and this excipient can together with the active component of the therapeutic combination that combines).
Embodiment 3
Provide about 180ml deionized water in room temperature.In this water, dissolve approximately 20 grams of citric acids.Like this, obtain 10% aqueous citric acid solution.
The microcrystalline Cellulose that acquisition is obtained commercially.Described microcrystalline Cellulose can derive from JRS PHARMA GmbH & Co.KF under trade name Vivapur101.The microcrystalline Cellulose of about 9.5g dried forms is provided in room temperature, and applies approximately 5 grams of 10% citric acid solutions by spraying to this dry particles.Use Nalgene Aerosol Spray Bottle Cat.No.2430-0200 that described citric acid solution is sprayed in described dry particles, described microgranule is mixed simultaneously, like this solution is put on to described microgranule equably.Then the mixture obtaining in drying at room temperature, to obtain having the desciccate of approximately 10 gram weight.The sample of the microcrystalline Cellulose obtaining and the intimate mixture of citric acid, for white, is made up of approximately 95 parts of microcrystalline Cellulose and approximately 5 parts of citric acids, and is that be dried, free-pouring, fine powdered material.The representational excipient obtaining be substantially pure (, described intimate mixture is made up of microcrystalline Cellulose and citric acid, and be substantially devoid of other excipient materials and this excipient can together with the active component of the therapeutic combination that combines).
Embodiment 4
Provide about 180ml deionized water in room temperature.In this water, dissolve sodium carbonate and the sodium bicarbonate (, approximately 10 grams of sodium carbonate and 10 grams of sodium bicarbonate) of equivalent.Like this, obtain the aqueous solution of 5% sodium carbonate and 5% sodium bicarbonate.
The microcrystalline Cellulose that acquisition is obtained commercially.Described microcrystalline Cellulose can derive from JRS PHARMA GmbH & Co.KF under trade name Vivapur101.The microcrystalline Cellulose of about 9.5g dried forms is provided in room temperature, and applies approximately 5 grams of sodium carbonate/bicarbonate aqueous solutions by spraying to this dry particles.Use Nalgene Aerosol Spray Bottle Cat.No.2430-0200 that described solution is sprayed in described dry particles, described microgranule is mixed simultaneously, like this solution is put on to described microgranule equably.Then the mixture obtaining in drying at room temperature, to obtain having the desciccate of approximately 10 gram weight.The sample of microcrystalline Cellulose, sodium bicarbonate and the intimate mixture of sodium carbonate obtaining, for white, is made up of approximately 95 parts of microcrystalline Cellulose, approximately 2.5 parts of sodium bicarbonate and approximately 2.5 parts of sodium carbonate, and is that be dried, free-pouring, fine powdered material.The representational excipient obtaining be substantially pure (, described intimate mixture is made up of microcrystalline Cellulose, sodium bicarbonate and sodium carbonate, and be substantially devoid of other excipient materials and this excipient can together with the active component of the therapeutic combination that combines).
Embodiment 5
Provide about 180ml deionized water in room temperature.In this water, dissolve approximately 20 grams of tertiary sodium phosphates.Like this, obtain 10% trisodium phosphate aqueous solution.
The microcrystalline Cellulose that acquisition is obtained commercially.Described microcrystalline Cellulose can derive from JRS PHARMA GmbH & Co.KF under trade name Vivapur101.The microcrystalline Cellulose of about 9g dried forms is provided in room temperature, and applies approximately 10 grams of 10% trisodium phosphate solutions by spraying to this dry particles.Use Nalgene Aerosol Spray Bottle Cat.No.2430-0200 that described trisodium phosphate solution is sprayed in described dry particles, described microgranule is mixed simultaneously, like this solution is put on to described microgranule equably.Then the mixture obtaining in drying at room temperature, to obtain having the desciccate of approximately 10 gram weight.The sample of the microcrystalline Cellulose obtaining and the intimate mixture of tertiary sodium phosphate, for white, is made up of approximately 90 parts of microcrystalline Cellulose and approximately 10 parts of tertiary sodium phosphates, and is that be dried, free-pouring, fine powdered material.The representational excipient obtaining be substantially pure (, described intimate mixture is made up of microcrystalline Cellulose and tertiary sodium phosphate, and be substantially devoid of other excipient materials and this excipient can together with the active component of the therapeutic combination that combines).
Embodiment 6
(for example use conventionally similar active component, nicotine Andrea Pollack phosphorus resin) and for the preparation of the ordinary excipients composition of commercially available chewing gum (for example, coloring agent, correctives, glycerol, chewing gum base and sorbitol) produce chewing gum, it is in shape and be conventionally similar in form and comprise 4mg nicotine and can be used as Nicorette Original Gum (by GlaxoSmithKline Consumer Healthcare, L.P. distribution) chewing gum that contains nicotine that is commercially available, but described in contain nicotine chewing gum in microcrystalline Cellulose/sodium carbonate mixture of being prepared according to embodiment 2 of sodium carbonate substitute.Enough microcrystalline Cellulose/sodium carbonate mixture are mixed in the chewing gum that contains nicotine, and the amount that contains the sodium carbonate from crystallite/sodium carbonate mixture in the chewing gum of nicotine described in making equals the amount of the sodium carbonate of original existence in the original formulation of improved, the not commercially available chewing gum that contains nicotine.Like this, provide a kind of compositions with gum formats, it comprises active component and the non-active ingredient with the intimate contact of microcrystalline Cellulose carrier material.
Embodiment 7
(for example use conventionally similar active component, nicotine Andrea Pollack phosphorus resin) and for the preparation of the ordinary excipients composition of commercially available chewing gum (for example, arabic gum, acesulfame-K, burn wax, coloring agent, correctives, chewing gum base, hydroxypropyl cellulose, magnesium oxide, sodium bicarbonate, Pulvis Talci, titanium dioxide and xylitol) produce coated chewing gum, it is in shape and be conventionally similar in form and comprise 4mg nicotine and can be used as the chewing gum that contains nicotine that Coated Nicotine Gum (being distributed by Walgreen Co.) is commercially available, but described in contain nicotine chewing gum in microcrystalline Cellulose/sodium carbonate mixture of being prepared according to embodiment 2 of sodium carbonate substitute.Enough microcrystalline Cellulose/sodium carbonate mixture are mixed in the chewing gum that contains nicotine, and the amount that contains the sodium carbonate from crystallite/sodium carbonate mixture in the chewing gum of nicotine described in making equals the amount of the sodium carbonate of original existence in the original formulation of improved, the not commercially available chewing gum that contains nicotine.
Embodiment 8
With producing coated chewing gum with the conventionally similar excipient composition for the preparation of commercially available chewing gum, it is in shape and be conventionally similar in form and comprise 4mg nicotine and can be used as the chewing gum that contains nicotine that Zonnic (being distributed by Niconovum AB) is commercially available, but described in contain nicotine chewing gum in microcrystalline Cellulose/sodium carbonate mixture of being prepared according to embodiment 2 of sodium carbonate substitute.Enough microcrystalline Cellulose/sodium carbonate mixture are mixed in the chewing gum that contains nicotine, and the amount that contains the sodium carbonate from crystallite/sodium carbonate mixture in the chewing gum of nicotine described in making equals the amount of the sodium carbonate of original existence in the original formulation of improved, the not commercially available chewing gum that contains nicotine.
Embodiment 9
With producing lozenge with the conventionally similar excipient composition for the preparation of commercially available lozenge, it is in shape and be conventionally similar in form and comprise 2mg nicotine and can be used as Nicotine Polacrilex Lozenge (by CVS Pharmacy, Inc. distribution) lozenge that contains nicotine that is commercially available, but described in contain nicotine lozenge in microcrystalline Cellulose/sodium carbonate mixture of being prepared according to embodiment 2 of sodium carbonate substitute.Enough microcrystalline Cellulose/sodium carbonate mixture are mixed in the lozenge that contains nicotine, and the amount that contains the sodium carbonate from crystallite/sodium carbonate mixture in the lozenge of nicotine described in making equals the amount of the sodium carbonate of original existence in the original formulation of improved, the not commercially available lozenge that contains nicotine.Like this, provide a kind of compositions with the form of lozenge, it comprises active component and the non-active ingredient with the intimate contact of microcrystalline Cellulose carrier material.
Embodiment 10
With similarly excipient composition and processing conditions are produced lozenge conventionally with lozenge for the preparation of setting forth in the table 1 of the embodiment 3 of the people's such as Axelsson U.S. Patent Publication No. 2010/0004294, it is in shape and be conventionally similar to the lozenge that contains nicotine that comprises 2.5mg nicotine in form, but described in contain nicotine lozenge in microcrystalline Cellulose/sodium carbonate mixture of being prepared according to embodiment 2 of sodium carbonate substitute.Enough microcrystalline Cellulose/sodium carbonate mixture are mixed in the lozenge that contains nicotine, and the amount that contains the sodium carbonate from crystallite/sodium carbonate mixture in the lozenge of nicotine described in making equals the amount of the sodium carbonate of original existence in the original formulation of the not improved lozenge that contains nicotine of quoting embodiment of described references.
Embodiment 11
With similarly excipient composition and processing conditions are produced lozenge conventionally with lozenge for the preparation of setting forth in the table 1 of the embodiment 3 of the people's such as Axelsson U.S. Patent Publication No. 2010/0004294, it is in shape and be conventionally similar to the lozenge that contains nicotine that comprises 2.5mg nicotine in form, but described in contain nicotine lozenge in microcrystalline Cellulose/sodium carbonate mixture of being prepared according to embodiment 2 of sodium carbonate substitute.Enough microcrystalline Cellulose/sodium carbonate mixture are mixed in the lozenge that contains nicotine, and the amount that contains the sodium carbonate from crystallite/sodium carbonate mixture in the lozenge of nicotine described in making equals the amount of the sodium carbonate of original existence in the original formulation of the not improved lozenge that contains nicotine of quoting embodiment of described references.
In addition, before contacting to form lozenge with other composition of lozenge, use described references quote embodiment in the mode usually set forth, with being dissolved in ethanol coated microcrystalline Cellulose/the sodium carbonate mixture of L100 coating material solution is also dry.Like this, the separate constituent that described lozenge contains the nicotine salt active component being adsorbed on microcrystalline Cellulose and the coating excipient form being made up of the sodium carbonate being adsorbed on microcrystalline Cellulose.
Embodiment 12
With with for the preparation of commercially available medicated bag, conventionally similarly medicated bag material, active component and excipient composition are produced Medicinal bag type product, it is in shape and be similar in form and can be used as the medicated bag that contains nicotine that Zonnic (being distributed by Niconovum A.B.) is commercially available, but microcrystalline Cellulose/tertiary sodium phosphate mixture replacing that the tertiary sodium phosphate of described Medicinal bag type product is prepared according to embodiment 5.Enough microcrystalline Cellulose/tertiary sodium phosphate mixture are mixed in the Medicinal bag type product that contains nicotine, in the Medicinal bag type product that makes to contain nicotine, equal the amount of the tertiary sodium phosphate of original existence in the original formulation of not improved, the Medicinal bag type product that contains nicotine that be obtained commercially from the amount of the tertiary sodium phosphate of crystallite/tertiary sodium phosphate mixture.
Embodiment 13
With with for the preparation of those Medicinal bag type products conventionally similarly excipient composition produce Medicinal bag type product, it is in shape and be similar to the medicated bag that contains nicotine of setting forth as Folium Nicotianae preparatum bag compositions J in the embodiment 1 of the people's such as Axelsson PCT WO 2007/104573 in form, but microcrystalline Cellulose/sodium carbonate/bicarbonate mixture replacing that the sodium carbonate in disclosed document and sodium bicarbonate are prepared according to embodiment 4.Enough microcrystalline Cellulose/sodium carbonate/bicarbonate mixtures are mixed in the Medicinal bag type product that contains nicotine, in the Medicinal bag type product that makes to contain nicotine, equal the sodium carbonate of original existence and the amount of sodium bicarbonate in the original formulation of the not improved Medicinal bag type product that contains nicotine of quoting embodiment of described references from the sodium carbonate of crystallite/sodium carbonate/bicarbonate mixture and the amount of sodium bicarbonate.

Claims (17)

1. a pharmaceutical composition that contains nicotine, it comprises:
Nicotine source; With
Porous carrier and the mixture that is adsorbed on the non-active ingredient on described porous carrier, described non-active ingredient is the form that is alkali or buffer agent,
Wherein said compositions is to be the mouth of described compositions or the pharmaceutically acceptable form that nose is sent of being suitable for.
2. pharmaceutical composition according to claim 1, wherein said non-active ingredient is sodium carbonate, sodium bicarbonate or their combination.
3. pharmaceutical composition according to claim 1, wherein said non-active ingredient is tertiary sodium phosphate.
4. pharmaceutical composition according to claim 1, wherein said nicotine source is the form that is free alkali, salt, complex or solvate.
5. pharmaceutical composition according to claim 1, wherein said nicotine source is nicotine Andrea Pollack phosphorus resin.
6. pharmaceutical composition according to claim 1, wherein said nicotine source is to be free alkali form.
7. pharmaceutical composition according to claim 1, wherein said nicotine source is tartaric acid nicotine or nicotine bitartrate.
8. pharmaceutical composition according to claim 1, wherein said porous carrier comprises microcrystalline Cellulose.
9. pharmaceutical composition according to claim 1, wherein said nicotine source is to be free alkali form, and described nicotine free alkali is attracted on the second porous carrier.
10. pharmaceutical composition according to claim 1, wherein said compositions is to be the form that is suitable for oral absorption.
11. pharmaceutical compositions according to claim 10, wherein said compositions is to be the form that is selected from chewing gum, lozenge, tablet and medicated bag product.
12. pharmaceutical compositions according to claim 1, wherein said non-active ingredient is alkali or buffer agent or their combination cushioning within the scope of alkaline pH, and described porous carrier comprises microcrystalline Cellulose.
13. pharmaceutical compositions according to claim 1, the wherein gross weight based on described mixture, described mixture comprises at least about the described porous carrier of 70 % by weight and the described non-active ingredient of approximately 30 % by weight at the most.
14. pharmaceutical compositions according to claim 1, the mixture of wherein said porous carrier and non-active ingredient further comprises outer coatings.
15. pharmaceutical compositions according to claim 1, wherein said nicotine source is selected from: the resin complexes of the nicotine of free alkali form, nicotine salt, nicotine, and composition thereof; Described non-active ingredient is alkali; And described compositions is the pharmaceutically acceptable form that is the oral absorption that is suitable for described compositions.
16. 1 kinds are used for the treatment of and have the method for the stimulation of nicotine sample acetylcholinergic receptor being made to the people experimenter of disease, disease or the obstacle of response, and described method comprises: give described people experimenter's per os or nasal administration effective dose according to the pharmaceutical composition described in any one in claim 1-15.
17. methods according to claim 16, wherein said step of applying comprises: use described pharmaceutical composition as smoking cessation adminicle to people experimenter.
CN201280060724.4A 2011-10-21 2012-10-19 Excipients for nicotine-containing therapeutic compositions Pending CN104114151A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US13/278,877 US9907748B2 (en) 2011-10-21 2011-10-21 Excipients for nicotine-containing therapeutic compositions
US13/278,877 2011-10-21
PCT/US2012/061023 WO2013059592A1 (en) 2011-10-21 2012-10-19 Excipients for nicotine-containing therapeutic compositions

Publications (1)

Publication Number Publication Date
CN104114151A true CN104114151A (en) 2014-10-22

Family

ID=47144140

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201280060724.4A Pending CN104114151A (en) 2011-10-21 2012-10-19 Excipients for nicotine-containing therapeutic compositions

Country Status (9)

Country Link
US (1) US9907748B2 (en)
EP (2) EP3744313A1 (en)
JP (1) JP6228544B2 (en)
CN (1) CN104114151A (en)
DK (1) DK2768479T3 (en)
ES (1) ES2811113T3 (en)
HU (1) HUE051459T2 (en)
PL (1) PL2768479T3 (en)
WO (1) WO2013059592A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110035669A (en) * 2016-12-30 2019-07-19 菲利普莫里斯生产公司 Sheet material containing nicotine and cellulose
CN114390922A (en) * 2019-09-18 2022-04-22 伊诺拉玛制药公司 Nicotine bag
CN114642271A (en) * 2020-12-17 2022-06-21 N·K·帕特尔 Nicotine pouch

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9763928B2 (en) * 2012-02-10 2017-09-19 Niconovum Usa, Inc. Multi-layer nicotine-containing pharmaceutical composition
US10034988B2 (en) 2012-11-28 2018-07-31 Fontem Holdings I B.V. Methods and devices for compound delivery
KR102320759B1 (en) 2013-05-06 2021-11-02 쥴 랩스, 인크. Nicotine salt formulations for aerosol devices and methods thereof
US10194693B2 (en) 2013-09-20 2019-02-05 Fontem Holdings 1 B.V. Aerosol generating device
US10357054B2 (en) 2013-10-16 2019-07-23 R.J. Reynolds Tobacco Company Smokeless tobacco pastille
CN113142679A (en) 2013-12-05 2021-07-23 尤尔实验室有限公司 Nicotine liquid formulations for aerosol devices and methods thereof
US11019840B2 (en) 2014-07-02 2021-06-01 R.J. Reynolds Tobacco Company Oral pouch products
US10959456B2 (en) 2014-09-12 2021-03-30 R.J. Reynolds Tobacco Company Nonwoven pouch comprising heat sealable binder fiber
US9968125B2 (en) 2015-01-09 2018-05-15 Philip Morris Products S.A. Nicotine—diketopiperazine microparticle formulations and methods of making the same
US10149844B2 (en) 2015-09-16 2018-12-11 Philip Morris Products S.A. Inhalable nicotine formulations, and methods of making and using thereof
US11224594B2 (en) 2015-09-16 2022-01-18 Philip Morris Products S.A. Nicotine formulations and methods of making and using the same
US9585835B1 (en) 2015-09-16 2017-03-07 Sansa Corporation (Barbados) Inc. Inhalable nicotine formulations and methods of making and using the same
US20170071248A1 (en) 2015-09-16 2017-03-16 Sansa Corporation (Barbados) Inc. System and Method for Controlling the Harshness of Nicotine-Based Dry Powder Formulations
US11297876B2 (en) 2017-05-17 2022-04-12 Rai Strategic Holdings, Inc. Aerosol delivery device
SE541358C2 (en) * 2017-05-30 2019-08-13 Enorama Pharma Ab Nicotine-containing chewing gum compositions
WO2018233795A1 (en) * 2017-06-23 2018-12-27 Fertin Pharma A/S Nicotine pouch
EP3641726A1 (en) * 2017-06-23 2020-04-29 MedCan Pharma A/S Cannabinoid pouch
CA3068089C (en) 2017-06-23 2022-09-13 Medcan Pharma A/S Cannabinoid pouch
US11793230B2 (en) 2019-12-09 2023-10-24 Nicoventures Trading Limited Oral products with improved binding of active ingredients
WO2021116842A1 (en) * 2019-12-09 2021-06-17 Nicoventures Trading Limited Oral products with controlled release
US11883527B2 (en) 2019-12-09 2024-01-30 Nicoventures Trading Limited Oral composition and method of manufacture
US11872231B2 (en) 2019-12-09 2024-01-16 Nicoventures Trading Limited Moist oral product comprising an active ingredient
US11889856B2 (en) 2019-12-09 2024-02-06 Nicoventures Trading Limited Oral foam composition
US11826462B2 (en) 2019-12-09 2023-11-28 Nicoventures Trading Limited Oral product with sustained flavor release
CA3160750A1 (en) 2019-12-09 2021-06-17 Anthony Richard Gerardi Oral product comprising a cannabinoid
US11617744B2 (en) 2019-12-09 2023-04-04 Nico Ventures Trading Limited Moist oral compositions
US11672862B2 (en) 2019-12-09 2023-06-13 Nicoventures Trading Limited Oral products with reduced irritation
US20220087997A1 (en) * 2020-09-22 2022-03-24 Fertin Pharma A/S Oral Antagonist Compositions For Nicotine Burning Relief
US11839602B2 (en) 2020-11-25 2023-12-12 Nicoventures Trading Limited Oral cannabinoid product with lipid component

Family Cites Families (134)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2033909A (en) 1934-12-19 1936-03-17 Niacet Chemicals Corp Manufacture of calcium levulinate
US3901248A (en) 1970-07-22 1975-08-26 Leo Ab Chewable smoking substitute composition
US3877468A (en) 1970-07-22 1975-04-15 Leo Ab Chewable tobacco substitute composition
US3845217A (en) 1972-11-16 1974-10-29 Helsingborg L Ab Buffered smoking substitute compositions
US4284809A (en) 1979-04-02 1981-08-18 The Upjohn Company 13,14-Didehydro-inter-oxa-19-oxo-PGF1 compounds
GB8301659D0 (en) 1983-01-21 1983-02-23 Leo Ab Smoking substitutes
US4655231A (en) 1984-01-09 1987-04-07 Advanced Tobacco Products, Inc. Snuff and preparation thereof
US4597961A (en) 1985-01-23 1986-07-01 Etscorn Frank T Transcutaneous application of nicotine
US4800903A (en) 1985-05-24 1989-01-31 Ray Jon P Nicotine dispenser with polymeric reservoir of nicotine
GB8615676D0 (en) 1986-06-26 1986-07-30 Stoppers Co Ltd Nicotine containing lozenge
US4830028A (en) 1987-02-10 1989-05-16 R. J. Reynolds Tobacco Company Salts provided from nicotine and organic acid as cigarette additives
IL86170A (en) 1987-05-01 1992-12-01 Elan Transdermal Ltd Preparations and compositions comprising nicotine for percutaneous administration
US5834011A (en) 1988-02-19 1998-11-10 The Regents Of The University Of California Method for aiding in the reduction of incidence of tobacco smoking
US5004610A (en) 1988-06-14 1991-04-02 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US5154927A (en) 1989-01-19 1992-10-13 Wm. Wrigley Jr. Company Gum composition containing dispersed porous beads containing active chewing gum ingredients and method
US5525351A (en) 1989-11-07 1996-06-11 Dam; Anders Nicotine containing stimulant unit
US5512306A (en) 1992-06-19 1996-04-30 Pharmica Ab Smoking substitute
SE8904295D0 (en) 1989-12-21 1989-12-21 Pharmacia Ab SMOKING SUBSTITUTE
US5167242A (en) 1990-06-08 1992-12-01 Kabi Pharmacia Aktiebolaq Nicotine-impermeable container and method of fabricating the same
US5147654A (en) 1990-07-23 1992-09-15 Alza Corporation Oral osmotic device for delivering nicotine
US5110605A (en) 1990-08-21 1992-05-05 Oramed, Inc. Calcium polycarbophil-alginate controlled release composition and method
JPH05255066A (en) 1991-04-25 1993-10-05 Takeda Chem Ind Ltd Composition for pharmaceutical preparation, its preparation and its production
GB9200047D0 (en) 1992-01-03 1992-02-26 Univ Alberta Nicotine-containing nasal spray
US6024097A (en) 1992-02-20 2000-02-15 J Mom Trust Product for assisting a smoker in giving up the habit
US6098632A (en) 1992-11-25 2000-08-08 Pharmacia & Upjohn Ab Nicotine-impermeable container and method of fabricating the same
US6602892B1 (en) 1993-06-10 2003-08-05 David P. L. Sachs Methods for nicotine replacement dosage determination
EP0708627B1 (en) 1993-07-09 2000-02-02 Cygnus, Inc. Method and device for providing nicotine replacement therapy transdermally/transbuccally
US5549906A (en) 1993-07-26 1996-08-27 Pharmacia Ab Nicotine lozenge and therapeutic method for smoking cessation
US5362496A (en) 1993-08-04 1994-11-08 Pharmetrix Corporation Method and therapeutic system for smoking cessation
SE9303574D0 (en) 1993-11-01 1993-11-01 Kabi Pharmacia Ab Composition for drug delivery and method of manufacturing thereof
IT1274034B (en) 1994-07-26 1997-07-14 Applied Pharma Res PHARMACEUTICAL COMPOSITIONS BASED ON RUBBER TO BE CHEWED AND PROCEDURE FOR THEIR PREPARATION
US5723477A (en) 1994-11-10 1998-03-03 Sibia Neurosciences, Inc. Modulators of acetylcholine receptors
US5604231A (en) 1995-01-06 1997-02-18 Smith; Carr J. Pharmaceutical compositions for prevention and treatment of ulcerative colitis
US5583140A (en) 1995-05-17 1996-12-10 Bencherif; Merouane Pharmaceutical compositions for the treatment of central nervous system disorders
US5811126A (en) 1995-10-02 1998-09-22 Euro-Celtique, S.A. Controlled release matrix for pharmaceuticals
DE69727922T2 (en) 1996-04-16 2005-01-20 Novartis Consumer Health S.A. QUICKLY CRACKING ORAL DOSAGE FORM
US6166048A (en) 1999-04-20 2000-12-26 Targacept, Inc. Pharmaceutical compositions for inhibition of cytokine production and secretion
GB9614902D0 (en) 1996-07-16 1996-09-04 Rhodes John Sustained release composition
DE19646392A1 (en) 1996-11-11 1998-05-14 Lohmann Therapie Syst Lts Preparation for use in the oral cavity with a layer containing pressure-sensitive adhesive, pharmaceuticals or cosmetics for dosed delivery
US5811442A (en) 1997-02-21 1998-09-22 Bencherif; Merouane Pharmaceutical compositions for the treatment of conditions associated with decreased blood flow
US6024981A (en) 1997-04-16 2000-02-15 Cima Labs Inc. Rapidly dissolving robust dosage form
US7214686B2 (en) 1997-06-30 2007-05-08 Targacept, Inc. Pharmaceutical compositions and methods for effecting dopamine release
US20030176467A1 (en) 1997-09-25 2003-09-18 Sven Andersson Nicotine compositions
US6268386B1 (en) 1998-06-25 2001-07-31 Marshall Anlauf Thompson Nicotine beverage
US6234169B1 (en) 1998-08-14 2001-05-22 Arthur Slutsky Inhaler
US6358060B2 (en) 1998-09-03 2002-03-19 Jsr Llc Two-stage transmucosal medicine delivery system for symptom relief
US20020098264A1 (en) 1998-11-27 2002-07-25 Cherukuri Subraman R. Medicated chewing gum delivery system for nicotine
US6344222B1 (en) 1998-09-03 2002-02-05 Jsr Llc Medicated chewing gum delivery system for nicotine
US6596298B2 (en) 1998-09-25 2003-07-22 Warner-Lambert Company Fast dissolving orally comsumable films
SE9803986D0 (en) 1998-11-23 1998-11-23 Pharmacia & Upjohn Ab New compositions
GB9826192D0 (en) 1998-12-01 1999-01-20 Controlled Theraputics Scotlan Oral transmucosal delivery
US7163705B2 (en) 1998-12-15 2007-01-16 Wm. Wrigley Jr. Company Coated chewing gum product and method of making
ATE288256T1 (en) 1999-01-14 2005-02-15 Noven Pharma DERMAL COMPOSITIONS
US6248363B1 (en) 1999-11-23 2001-06-19 Lipocine, Inc. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US7374779B2 (en) 1999-02-26 2008-05-20 Lipocine, Inc. Pharmaceutical formulations and systems for improved absorption and multistage release of active agents
US6090401A (en) 1999-03-31 2000-07-18 Mcneil-Ppc, Inc. Stable foam composition
US6426090B1 (en) 1999-04-06 2002-07-30 Wm. Wrigley Jr. Company Over-coated product including tableted center and medicament
US6322806B1 (en) 1999-04-06 2001-11-27 Wm. Wrigley Jr. Company Over-coated chewing gum formulations including tableted center
US6773716B2 (en) 1999-04-06 2004-08-10 Wm. Wrigley Jr. Company Over-coated chewing gum formulations
US6355265B1 (en) 1999-04-06 2002-03-12 Wm. Wrigley Jr. Company Over-coated chewing gum formulations
US6248760B1 (en) 1999-04-14 2001-06-19 Paul C Wilhelmsen Tablet giving rapid release of nicotine for transmucosal administration
US6583160B2 (en) 1999-04-14 2003-06-24 Steve Smith Nicotine therapy method and oral carrier for assuaging tobacco-addiction
US20010016593A1 (en) 1999-04-14 2001-08-23 Wilhelmsen Paul C. Element giving rapid release of nicotine for transmucosal administration
US6319510B1 (en) 1999-04-20 2001-11-20 Alayne Yates Gum pad for delivery of medication to mucosal tissues
GB9911037D0 (en) 1999-05-13 1999-07-14 Micap Limited Nicotine delivery service
US8256433B2 (en) 1999-07-16 2012-09-04 Aradigm Corporation Systems and methods for effecting cessation of tobacco use
US20080138398A1 (en) 1999-07-16 2008-06-12 Aradigm Corporation Dual release nicotine formulations, and systems and methods for their use
US6799576B2 (en) 1999-07-16 2004-10-05 Aradigm Corporation System for effecting smoking cessation
AU777326B2 (en) 1999-07-16 2004-10-14 Aradigm Corporation System for effecting smoke cessation
US6322828B1 (en) 1999-09-13 2001-11-27 Deseret Laboratories, Inc. Process for manufacturing a pharmaceutical chewing gum
US6660754B1 (en) 2000-02-15 2003-12-09 Smithkline Beecham Corporation Method for reducing or eliminating smoking
US7115297B2 (en) 2000-02-22 2006-10-03 Suzanne Jaffe Stillman Nutritionally fortified liquid composition with added value delivery systems/elements/additives
US7067116B1 (en) 2000-03-23 2006-06-27 Warner-Lambert Company Llc Fast dissolving orally consumable solid film containing a taste masking agent and pharmaceutically active agent at weight ratio of 1:3 to 3:1
US6596740B2 (en) 2000-10-24 2003-07-22 Richard L. Jones Nicotine mucosal spray
CN101301275A (en) 2001-03-26 2008-11-12 史密丝克莱恩比彻姆公司 Method for preparing nicotine containing oral dosage form
FR2823974B1 (en) 2001-04-25 2004-10-15 Pf Medicament SLOW RELEASE MEDICINAL LABEL FOR THE ACTIVE INGREDIENT
SE0102197D0 (en) 2001-06-20 2001-06-20 Pharmacia Ab New product and use and manufacture thereof
US6585997B2 (en) 2001-08-16 2003-07-01 Access Pharmaceuticals, Inc. Mucoadhesive erodible drug delivery device for controlled administration of pharmaceuticals and other active compounds
US7208186B2 (en) 2001-09-18 2007-04-24 Spi Pharma, Inc. Chewing gum formulation and method of making the same
BR0214820A (en) 2001-12-10 2005-08-30 Joseph Robert Knight Nicotine Treated Drink
SE0104388D0 (en) 2001-12-27 2001-12-27 Pharmacia Ab New formulation and use and manufacture thereof
US20030159702A1 (en) 2002-01-21 2003-08-28 Lindell Katarina E.A. Formulation and use manufacture thereof
WO2003066029A2 (en) 2002-02-07 2003-08-14 Pharmacia Corporation Pharmaceutical dosage form for mucosal delivery
EP1478646A1 (en) 2002-02-20 2004-11-24 PHARMACIA & UPJOHN COMPANY Azabicyclic compounds with alfa7 nicotinic acetylcholine receptor activity
US7105173B1 (en) 2002-03-21 2006-09-12 Rolling Kenneth J Nicotine replacement applique
US20040101543A1 (en) 2002-03-22 2004-05-27 John Liu Nicotine-containing oral dosage form
SE0201669D0 (en) 2002-06-03 2002-06-03 Pharmacia Ab New formulation and use thereof
US7767698B2 (en) 2002-06-03 2010-08-03 Mcneil Ab Formulation and use thereof
US8216609B2 (en) 2002-08-05 2012-07-10 Torrent Pharmaceuticals Limited Modified release composition of highly soluble drugs
US7135484B2 (en) 2002-08-14 2006-11-14 Abbott Laboratories Azabicyclic compounds are central nervous system active agents
US20040052851A1 (en) 2002-09-16 2004-03-18 Graff Allan H. Modified release oral dosage form
ATE407568T1 (en) 2002-09-24 2008-09-15 Gumlink As LOW MOISTURE CHEWING GUM
JP4343840B2 (en) 2002-09-24 2009-10-14 ガムリンク エー／エス Chewing gum with improved release of chewing gum ingredients
US8591967B2 (en) 2002-09-24 2013-11-26 Gumlink A/S Biodegradable chewing gum comprising at least one high molecular weight biodegradable polymer
JP4339792B2 (en) 2002-09-24 2009-10-07 ガムリンク エー／エス Chewing gum
FI3473251T3 (en) * 2002-12-20 2024-01-09 Niconovum Ab A nicotine-cellulose combination
WO2004064811A1 (en) 2003-01-24 2004-08-05 Magle Holding Ab A composition material for transmucosal delivery
EP1449525A1 (en) 2003-02-20 2004-08-25 Cross Chem Llc chewing gum in the form of multi-layer tablets
US20040182403A1 (en) 2003-02-28 2004-09-23 Sven-Borje Andersson Container comprising nicotine and the use and manufacture thereof
CN100381083C (en) 2003-04-29 2008-04-16 韩力 Electronic nonflammable spraying cigarette
PL2446881T3 (en) 2003-07-24 2014-08-29 Glaxosmithkline Llc Orally Dissolving Films
GB0320854D0 (en) 2003-09-05 2003-10-08 Arrow No 7 Ltd Buccal drug delivery
ATE422355T1 (en) 2003-09-08 2009-02-15 Mcneil Ab NICOTINE FORMULATIONS AND THEIR USE
US20050123502A1 (en) 2003-10-07 2005-06-09 Chan Shing Y. Nicotine containing oral compositions
US8741935B2 (en) 2003-12-02 2014-06-03 Fertin Pharma A/S Nicotine delivery product and method for producing it
US20060018840A1 (en) 2004-06-28 2006-01-26 Nektar Therapeutics Aerosolizable formulation comprising nicotine
ES2393191T3 (en) 2004-11-30 2012-12-19 Fertin Pharma A/S Method to provide quick relief to a consumer of a nicotine gum
US20090023819A1 (en) 2005-03-22 2009-01-22 Anders Axelsson Use of an Artificial Sweetener to Enhance Absorption of Nicotine
US8323683B2 (en) 2005-05-18 2012-12-04 Mcneil-Ppc, Inc. Flavoring of drug-containing chewing gums
DE602006010542D1 (en) 2005-06-01 2009-12-31 Fertin Pharma As METHOD FOR PRODUCING A PRODUCT TO BE NICOTIZED
EP1998755A2 (en) 2006-03-16 2008-12-10 NicoNovum AB Chewing gum compositions providing rapid release of nicotine
WO2007104573A2 (en) 2006-03-16 2007-09-20 Niconovum Ab Improved snuff composition
US20070269492A1 (en) 2006-05-16 2007-11-22 Per Steen New product and use and manufacture thereof
US20070269386A1 (en) 2006-05-16 2007-11-22 Per Steen New product and use and manufacture thereof
US8642016B2 (en) 2006-07-21 2014-02-04 Jsrnti, Llc Medicinal delivery system, and related methods
BRPI0716995A2 (en) 2006-09-27 2013-10-15 Niconovum Ab METHODS FOR ORAL ADMINISTRATION OF A LIQUID, AND FOR APPLICATION OF LIQUID TREATS OR ATOMIZED LIQUID CONTAINING AN ACTIVE SUBSTANCE WITHIN ANY INDIVIDUAL MOUTH, DEVICE, KIT, USE, KIT, USE
BRPI0719428A2 (en) 2006-12-01 2014-02-25 Cima Labs Inc SOLID ORAL TRANSMUCOSAL DOSAGE FORM, METHOD FOR TREATING NICOTINE DEPENDENCE IN A RECEIVER WISHING SUCH TREATMENT, ORAL TRANSMUCOSAL NICOTINE DISTRIBUTION, AND NICOTINE REPLACEMENT METHOD.
US20080286340A1 (en) 2007-05-16 2008-11-20 Sven-Borje Andersson Buffered nicotine containing products
US20080286341A1 (en) 2007-05-16 2008-11-20 Sven-Borje Andersson Buffered coated nicotine containing products
US20080292683A1 (en) 2007-05-24 2008-11-27 Monosolrx, Llc. Film shreds and delivery system incorporating same
US20090004248A1 (en) 2007-06-29 2009-01-01 Frank Bunick Dual portion dosage lozenge form
WO2009037319A2 (en) 2007-09-18 2009-03-26 Niconovum Ab Stable chewing gum compositions comprising maltitol and providing rapid release of nicotine
US20090081291A1 (en) 2007-09-26 2009-03-26 Gin Jerry B Sustained Release Dosage Forms For Delivery of Agents to an Oral Cavity of a User
EP2229159A2 (en) 2007-12-11 2010-09-22 Novartis AG Multi-zone films
WO2009143347A2 (en) 2008-05-22 2009-11-26 Teva Pharmaceutical Industries Ltd. Varenicline tosylate, an intermediate in the preparation process of varenicline l-tartrate
US20100018539A1 (en) 2008-07-28 2010-01-28 Paul Andrew Brinkley Smokeless tobacco products and processes
JP2012505878A (en) 2008-10-14 2012-03-08 マクニール アーベー Multiple partial oral dosage forms and uses thereof
EP2233134A1 (en) 2009-03-27 2010-09-29 McNeil AB Multi-portion intra-oral dosage form with organoleptic properties
US20100247586A1 (en) * 2009-03-27 2010-09-30 Andreas Hugerth Multi-Portion Intra-Oral Dosage Form With Organoleptic Properties
US20100256197A1 (en) 2009-04-02 2010-10-07 Silver Eagle Labs Nv, Llc Nicotine Dissolving Film With Or Without Menthol
KR101138851B1 (en) 2009-04-27 2012-05-09 김만규 nonsmoking gum composition and preparing method thereof
US20110070286A1 (en) * 2009-09-24 2011-03-24 Andreas Hugerth Process for the manufacture of nicotine-comprising chewing gum and nicotine-comprising chewing gum manufactured according to said process
US20110268809A1 (en) 2010-04-28 2011-11-03 Paul Andrew Brinkley Nicotine-Containing Pharmaceutical Compositions
US20110274628A1 (en) 2010-05-07 2011-11-10 Borschke August J Nicotine-containing pharmaceutical compositions

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110035669A (en) * 2016-12-30 2019-07-19 菲利普莫里斯生产公司 Sheet material containing nicotine and cellulose
CN110035669B (en) * 2016-12-30 2022-02-18 菲利普莫里斯生产公司 Sheet material containing nicotine and cellulose
US11758937B2 (en) 2016-12-30 2023-09-19 Philip Morris Products S.A. Nicotine and cellulose containing sheet
CN114390922A (en) * 2019-09-18 2022-04-22 伊诺拉玛制药公司 Nicotine bag
CN114642271A (en) * 2020-12-17 2022-06-21 N·K·帕特尔 Nicotine pouch

Also Published As

Publication number Publication date
EP2768479B1 (en) 2020-07-15
US20130098377A1 (en) 2013-04-25
EP2768479A1 (en) 2014-08-27
US9907748B2 (en) 2018-03-06
ES2811113T3 (en) 2021-03-10
JP2014530871A (en) 2014-11-20
DK2768479T3 (en) 2020-08-10
WO2013059592A1 (en) 2013-04-25
PL2768479T3 (en) 2020-12-28
HUE051459T2 (en) 2021-03-01
EP3744313A1 (en) 2020-12-02
JP6228544B2 (en) 2017-11-08

Similar Documents

Publication Publication Date Title
CN104114151A (en) Excipients for nicotine-containing therapeutic compositions
US9937168B2 (en) Nicotine-containing pharmaceutical compositions
JP5981416B2 (en) Nicotine-containing pharmaceutical composition
CA2683436C (en) Melatonin tablet and methods of preparation and use
JP4708795B2 (en) Physically and chemically stable nicotine-containing particulate matter
US20090136569A1 (en) Rapidly disintergrating tablet in oral cavity
CN103476372A (en) Sublingual films
JP2010526876A (en) Coated oral nicotine formulation buffered by amino acids
JP2009114113A (en) Intraorally disintegrable tablet and method for producing the same
JP2009529561A (en) Stable lozenge composition providing rapid release of nicotine
KR20160108828A (en) Rapidly disintegrating formulations and methods of use
JP2007509031A (en) Galantamine oral formulation and use thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20141022